CYCLIC PEPTIDE DERIVATIVE, METHOD FOR PREPARING SAME AND COMPOSITION THEREOF
|Posted date||Aug 9, 2016|
|International application number||2015JP076797|
|International publication number||WO 2016047638|
|Date of international filing||Sep 18, 2015|
|Date of international publication||Mar 31, 2016|
|Title||CYCLIC PEPTIDE DERIVATIVE, METHOD FOR PREPARING SAME AND COMPOSITION THEREOF|
|Abstract||Provided is: a cyclic peptide derivative which is derived from Paecilomyces tenuipes having an astrocyte proliferative activity; or a salt thereof.|
|Outline of related art and contending technology||
Insects are vertebrate or invertebrate, or vertebrate that is different from the immune system comprises a metabolic pathway, in vivo synthesis of various physiologically active substance and a strong innate immunity in resistance to pathogens and virus exhibits. In addition, insects, such as biology, and the outside, for example, other organisms, pathogens, specific relationship between the virus and the like are formed. For this reason, in recent years, the biologically active substances derived from insects user, is proceeding and research, has not been known in the art that the compound having a novel construction of the large number have been discovered.
The present inventors have found, as part of such a background, so far, the pharmacological effects of the insects and the like have been studied.
The name of the category of the insects, more traditional form of the conventional mating ability as a center, ecological, pathogenic, indicator representation such as a chemical class, the relationship between the overall system discussed above, has been designated. At present, an indicator molecule genotype classification system, the relationship between the genus Cordyceps bakkakukin family and review in the system, taking into consideration also the morphological feature constructed new classification, have been proposed. Therefore, in the following description is, pictorial book user, insects (2014 years, as grains Co.) based on the description of the described japanese name of insects, not the first mention, conventional type name in parenthesis, as in a new classification species name.
Is such insects, insects and insect obsess one of phytopathogenic fungi, in a narrow sense interpretation, insect (Insecta) network, the first Zhou (Lepidoptera), finger superfamily Bat (Hepialoidea), belonging to the family Bat (Hepialidiae) finger and finger Bat Chinese tibet host treated with the autonomy, saving qinghai, saving four river, saving noble state, Shaanxi saving, including saving yunnan, 4,000 or 3,000 for a fuel cell in the elevation of the meter from Kashmir alpine area on live to sinensis touchuukasou also referred to as (Cordyceps sinennsis, Ophiocordyceps sinennsis) means. Also various types of host insect, stink bug (Hemiptera) first, the second (Lepidoptera) Zhou, Coleoptera first, the second honeycomb (Hymenoptera), grasshoppers (Orthoptera) first, the second register marks (Odonata), the first wide-fly (Diptera).
On the other hand, is understood in a broad sense, such insect larvae or adult insects parasitic fungi as a whole are referred to.
Then, for insects, as a material for health food supplement Chinese herb material of the scientific findings suggest that in early stage, the physiological activity of the insects to this study as an example, diabetes or its products sinensis touchuukasou, prevent cardiovascular disease or metabolic disease or cancer, or, delaying of the progression of their disease pharmacologically effective are widely used as a (non-patent document 1). In addition to this, the water extract of bamboo (Cordyceps militaris) pupa (non-patent document 2) anti-oxidant action, the modulatory effects (non-patent document 3), and in vivo decrease in insulin resistance in insulin secretion (non-patent document 4) of increasing effect, in the production of tibet sinensis touchuukasou insects by hot-water extraction of the anti-hyperlipidemia effect (non-patent document 5), anti-tumor activity (non-patent document 6), anti-inflammatory effects (non-patent document 7) and the like have been reported. In addition, also in the most recent, isolated from sinensis touchuukasou cordycepin for physiologically active substances and the like, has not been previously reported to have a new physiological activity and the like have been reported (non-patent document 8-10) then, mentions of such insects due to an increase in demand due to rapid increase of such as by overfishing, availability of tibet sinensis touchuukasou production difficult and expensive.
In addition, as the best interpretation of the insects in a broad sense one of hanasanagitake (Paecilomyces tenuipes, Isaria japonica Yasuda also referred to as 1) is, cordyceps include fungi belonging to genus Cordyceps of family, silkworm (Bombyx mori, hereinafter referred to as b. mori) larvae and pupae from parasitic fungi in, silkworm pupae of insects by the combination of the artificial cultivation are commercialized in Japan in recent years. However, commercially available Cordyceps genus Paecilomyces genus and many of the insects of the genus Isaria and the article of commerce of asexual mycelial culture prepared from one of many that were, further, reports a study concerning the effect of pharmacological hanasanagitake overwhelmingly smaller than sinensis touchuukasou.
Up to now, as the physiologically active component of the hanasanagitake, cereal, or cereal and yeast or extracts thereof were cultivated in medium supplemented with dry powder and fruiting hanasanagitake, methanol extract 70%, partitioned water - ethyl acetate, the aqueous phase was partitioned water - n - butanol, n- butanol phases were chromatographed over silica gel, eluting with ethyl acetate to obtained spiro tenui pesin A, B is known (patent document 1). In addition, a host (silkworm pupae) and the ethyl acetate extract of mixed powder of the fruiting in cyclic hexadepsipeptides peptide isolated from a rat liver cancer cell growth Beauvericin has an inhibitory effect (non-patent document 11) and, separated from the host (silkworm pupae) fruiting body material, 60% ethanol extraction, methanol extract 5%, hot-water extraction through the processes of the (3, 4 - - DOPA di guanidino butanoylamino) hanasanagin is obtained, erase activity and superoxide anion free radicals (DPPH) have the ability to be erased (non-patent document 12, 13) and the like are known.
Then, the inventors of the present invention, is easily obtainable and compared with the sinensis touchuukasou, cost, is excellent in terms of a stable supply of advances in the studies on the hanasanagitake, hanasanagitake extract fractions derived from the powder, and the mammalian brain function improvement, significant astrocyte growth promoting activity are found (Patent Document 2, 3). Therefore, the inventors of the present invention, subsequently, the associations and hanasanagitake astrocytes and proliferative activity, has been studied further.
Which is a kind of glial cells (astrocytes) astrocytes is, about half of the cells occupies all of the brain. Conventionally, from the viewpoint of the information processing function is responsible for the nerve cells, nerve cells as a function of the present around the astrocytes, a neural cell of a support, protection, and the like have been considered to nutrient supply.
On the other hand, in recent years, the astrocytes, neural forming function (non-patent document 14-17), transfer material concentration adjusting function (non-patent document 18, 19) indirect that auxiliary mechanism using the neural circuit formation, followed by nerve cells and an input from the calcium propagation between the astrocytes (non-patent document 20-22), comprises a synaptic vesicle can be output to nerve cells (non-patent document 23, 24) reported such as the start of the, astrocytes are responsible for the wing to the information processing of the cell itself has been suggested.
Further, the role of astrocytes to the formation of the storage begun studies are underway, the storage of higher functions of the brain, neurons and astrocytes via interaction between the controlled and is considered to be in the barrier layer. For example, memory formation after an increase in the number of astrocytes in the hippocampus (non-patent document 25) or, inhibiting the function of astrocytes and the memory can interfere with the formation and the like (non-patent document 26) have been reported.
In addition, conventional, bipolar disorder or schizophrenia, mental disorders such as depression commonly found in cranial nerve anatomical anomalies, macro-level in the ventricular hypertrophy, hippocampus, observed by reducing the size of the cerebral cortex, a micro level with the reduced size of neuronal cell bodies, a decrease in dendritic spine density, shortening the length of the dendrites, synapse-associated protein have been known for the reduction of the amount. These direct neuronal cells have been considered to be abnormal. However, in recent years, reduction in the number of astrocytes also commonly observed and reported that, based on the decrease in the number of astrocytes indirectly the possibility of abnormality of the state of neuronal cells has been studied (non-patent document 27).
|Scope of claims||
|IPC(International Patent Classification)||
National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KN KP KR KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
Contact Information for " CYCLIC PEPTIDE DERIVATIVE, METHOD FOR PREPARING SAME AND COMPOSITION THEREOF "
- Iwate University Center for Regional Collaboration in Research and Education
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- Address: 4-3-5 Ueda Moriokashi Iwateken, Japan , 020-8551
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